rs7717955

Variant names:

• chr5-35862739-C-T
• rs7717955
• NM_002185.5:c.221+1749C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002185.5(IL7R):​c.221+1749C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,936 control chromosomes in the GnomAD database, including 4,295 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4295 hom., cov: 31)
• Consequence: IL7R NM_002185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 27 publications found

Genes affected

IL7R (HGNC:6024): (interleukin 7 receptor) The protein encoded by this gene is a receptor for interleukin 7 (IL7). The function of this receptor requires the interleukin 2 receptor, gamma chain (IL2RG), which is a common gamma chain shared by the receptors of various cytokines, including interleukins 2, 4, 7, 9, and 15. This protein has been shown to play a critical role in V(D)J recombination during lymphocyte development. Defects in this gene may be associated with severe combined immunodeficiency (SCID). Alternatively spliced transcript variants have been found. [provided by RefSeq, Dec 2015]

IL7R Gene-Disease associations (from GenCC):

• immunodeficiency 104

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL7R	NM_002185.5	c.221+1749C>T		intron_variant	Intron 2 of 7	ENST00000303115.8	NP_002176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL7R	ENST00000303115.8	c.221+1749C>T		intron_variant	Intron 2 of 7	1	NM_002185.5	ENSP00000306157.3

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34904 AN: 151818 Hom.: 4295 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 34925 AN: 151936 Hom.: 4295 Cov.: 31 AF XY: 0.232 AC XY: 17192 AN XY: 74252

African (AFR) AF: 0.166 AC: 6861 AN: 41456

American (AMR) AF: 0.184 AC: 2811 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 837 AN: 3464

East Asian (EAS) AF: 0.195 AC: 1005 AN: 5166

South Asian (SAS) AF: 0.200 AC: 965 AN: 4818

European-Finnish (FIN) AF: 0.346 AC: 3647 AN: 10540

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18030 AN: 67928

Other (OTH) AF: 0.205 AC: 433 AN: 2112

Alfa AF: 0.246 Hom.: 13066

Bravo AF: 0.217

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7717955; hg19: chr5-35862841;